In collaboration with Dr. Stephen Dewhurst at the University of Rochester, we have been examining the immunopathology of acute SIVsmmPBj infection in macaques. Our research has focused on the mechanism of acute disease development. Previous studies of ours have shown that animals developing acute disease following SIVsmmPBj infection show increased levels of apoptosis and upregulation of an intestinal-specific integrin. New results have shown that this virus induces an increased level of Fas ligand expression and requires co-stimulatory molecules for inducing PBMC activation. Taken together these data strongly suggest that immune activation is an important element in PBj pathogenesis. FUNDING NIH / AI 39397 $83,143 4/01/96 - 3/31/99 PUBLICATIONS Hodge, S.M., Novembre, F.J. and Dewhurst, S. Endogenous tumor necrosis factor-( contributes to lymphoproliferation induced by simian immunodeficiency virus variant, SIVsmmPBj14. Immunol Lett 63:49-51, 1998. Hodge, S., Novembre, F.J., Whetter, L., Gelbard, H.A. and Dewhurst, S. Induction of fas ligand expression by an acutely lethal simian immunodeficiency virus, SIVsmmPBj14. Virol 252(2):354-363, 1998. Whetter, L., Novembre, F.J., Saucier, M.M., Gummuluru, S. and Dewhurst, S. Costimulatory pathways in lymphocyte proliferation induced by simian immunodeficiency virus, SIVsmmPBj14. J Virol 72:6155-6158, 1998. P51RR00165-38 1/1/1998 - 12/31/1998 Yerkes Regional Primate Research Center